Hua Medicine recently announced the positive results of the world ’s first dual mechanism glucokinase activator dorzagliatin (HMS5552) clinical study HMM0112.
HMM0112 is a phase I trial in the United States conducted in patients with type 2 diabetes who were treated with metformin, DPP-4 inhibitors, or SGLT-2 inhibitors alone or in combination but had insufficient glycemic control. The main purpose was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of dorzagliatin and empagliflozin (an SGLT-2 inhibitor) as monotherapy or combination therapy. PK results showed that dorzagliatin (75 mg BID [2 times a day]) and empagliflozin (25 mg QD [1 time a day]) had no effect on their respective PK characteristics when co-administered, supporting their combined clinical application, and PD results show that the efficacy of combination therapy has obvious synergistic effect.
In the oral glucose tolerance test (OGTT), the hypoglycemic effect of the combined treatment group (AUEC: 279h • mg / dL) was significantly better than that of englitazone monotherapy (AUEC: 452h • mg / dL, p <0.01) Dorzagliatin monotherapy (AUEC: 364h • mg / dL, p <0.05). In addition, the C-peptide secretion of the combination therapy was also significantly higher than that of englitinine monotherapy. These results support the development of the combined treatment of dorzagliatin and englitin, which will provide better efficacy and better solutions for patients with type 2 diabetes.
Currently, there are 435 million people with type 2 diabetes worldwide. Diabetes imposes a huge medical burden on the global medical system. Existing diabetes therapies cannot effectively control the deterioration of the disease, leading to various complications in patients with post-diabetes, such as vision loss, peripheral neuropathy, impaired kidney function, and heart Vascular disease and stroke.
Dorzagliatin is the world's first dual-acting glucokinase activator (GKA), which aims to control the development of progressive degenerative diseases of diabetes by restoring glucose homeostasis in patients with type 2 diabetes. By repairing the defect of the glucose sensor function of glucokinase, dorzagliatin has the potential to restore the impaired blood glucose homeostasis of type 2 diabetes patients, and can be used as a first-line treatment standard for the treatment of the disease, or as a combination with currently approved anti-diabetic drugs Basic treatment used.
Dr. Chen Li, CEO of Hualing Pharmaceutical, said: "SGLT-2 inhibitors are a relatively new class of oral drugs for the treatment of type 2 diabetes; in addition to controlling blood sugar, these drugs have also been found to have blood pressure and weight loss The global sales in 2019 are about 6 billion US dollars. The positive result of the HMM0112 study shows that the addition of dorzagliatin on the basis of SGLT-2 inhibitors can enhance the blood sugar control of patients with type 2 diabetes, thereby expanding the applicable population of patients. It also shows a synergistic effect of restoring islet function. This successful result will advance our mission to provide dorzagliatin as a monotherapy or in combination with the currently approved best-selling oral hypoglycemic agents. At present, we have proved that dorzagliatin is combined with Westa Sitagliptin (a DPP-4 inhibitor, the world's best-selling oral hypoglycemic agent) and metformin (a global first-line oral hypoglycemic agent) have similar positive results. In this way, our goal is to be type 2 Diabetes patients provide a completely new treatment, through dorzagliatin monotherapy or in combination with currently available diabetes Method to prevent or delay the onset of diabetes and its complications. "
In November 2019, Hualing Pharmaceuticals announced the 24-week top-line results of dorzagliatin's first phase III clinical study (HMM0301, NCT03173391). The company will announce the top 52-week key results of the HMM0301 research by the third quarter of this year. Currently, another phase III registered clinical trial (HMM0302) evaluating the combined treatment of dorzagliatin and metformin for type 2 diabetes has completed 24 weeks of follow-up. Hualing Pharmaceutical plans to publish the key findings of the study for 24 weeks before the third quarter of this year, and The 52-week key results will be announced before the end of the year. In January this year, Hualing Pharmaceutical also announced the ideal results of a phase I clinical study (HMM0111) of dorzagliatin combined with sitagliptin (sitagliptin, a DPP-4 inhibitor) for the treatment of type 2 diabetes, confirming that dorzagliatin and Sieg The clinical advantages and potential synergies of the combination of leutin. In addition, the positive result of another phase I clinical study (HMM0110) shows the potential of dorzagliatin in type 2 diabetes patients with advanced chronic kidney disease.
The HMM0301 study included patients with type 2 diabetes who had never received diabetes medication. The first 24 weeks of the study were randomized, double-blind, placebo-controlled efficacy and safety studies. Patients were included in dorzagliatin or placebo in a 2: 1 ratio The group received dorzagliatin 75 mg twice a day or placebo. The investigator conducted follow-up every 4 weeks. The last 28 weeks of the study were open-label active drug safety studies. All patients received dorzagliatin 75 mg twice a day.
The data of the first 24 weeks of monotherapy showed that the study reached the main efficacy endpoint: after 24 weeks of treatment, the glycated hemoglobin (HbA1c) in the dorzagliatin treatment group was reduced by 1.07% from the baseline of 8.35% (least squares average), and the placebo group from The baseline 8.37% was reduced by 0.5%. Compared with placebo group, the decrease of HbA1c in the dorzagliatin treatment group was statistically significant (p <0.0001).
According to the analysis results of the protocol data set, according to the American Diabetes Association's ADA treatment compliance standard (post-treatment HbA1c is less than 7%), 45.5% of the patients in the dorzagliatin treatment group met the standard, and the placebo group's compliance rate was 21.5%. Significant statistical significance (PPS, p <0.0001); composite endpoint of glucose homeostasis control rate, that is, HbA1c treatment reached the standard and no hypoglycemic event occurred at the same time, reaching 45% in the dorzagliatin group, significantly higher than the 21.5% compliance rate in the placebo group (P <0.0001). Dorzagliatin is well tolerated during 24 weeks of monotherapy.